Dale S M, Kuang R Z, Wei X, Varon S
Department of Biology, University of California, San Diego, La Jolla 92093-0506, USA.
Exp Neurol. 1995 Sep;135(1):67-73. doi: 10.1006/exnr.1995.1066.
Little is known about the neurotrophic factors that may regulate maintenance, growth, and/or repair of corticospinal motor neurons (CSMN) in the developing or the adult mammal. We have developed an adult rat in vivo model of CSMN injury involving (i) bilateral prelabeling of CSMN with a cervical spinal cord injection of cholera toxin B subunit (CTB), (ii) unilateral axotomy close to the cell bodies by an intracortical lesion between cell layer V and the corpus callosum, and (iii) implantation of a continuous infusion device in the cortical parenchyma near the lesion. Two weeks later, coronal sections of the cortex are immunostained for CTB, and CTB-stained neurons are counted over defined section areas and compared to those on the contralateral (nonlesioned, noninfused) side. CTB-stainable neurons were 30-40% of the control side when the lesion was about 200 microns from the deeper face of the cell layer, and survival increased with increasing lesion depths. The model can be used to assess protective effects of potential CSMN trophic factors. The low survival achieved with the more superficial lesions (200 and 300 microns) was markedly improved by continuous infusion of ciliary neurotrophic factor at 0.1 to 1.0 microgram/day.
关于在发育中的或成年哺乳动物中可能调节皮质脊髓运动神经元（CSMN）的维持、生长和/或修复的神经营养因子，人们了解甚少。我们已经建立了一种成年大鼠CSMN损伤的体内模型，该模型包括：（i）通过颈脊髓注射霍乱毒素B亚基（CTB）对CSMN进行双侧预标记；（ii）通过在V层细胞和胼胝体之间进行皮质内损伤，在靠近细胞体处进行单侧轴突切断；（iii）在损伤附近的皮质实质内植入持续输注装置。两周后，对皮质的冠状切片进行CTB免疫染色，在确定的切片区域内对CTB染色的神经元进行计数，并与对侧（未损伤、未输注）的神经元进行比较。当损伤距离细胞层较深表面约200微米时，CTB可染色的神经元为对照侧的30%-40%，并且随着损伤深度的增加，神经元存活率升高。该模型可用于评估潜在的CSMN营养因子的保护作用。通过每天持续输注0.1至1.0微克的睫状神经营养因子，明显改善了较浅损伤（200和300微米）时较低的神经元存活率。
